The family of peptide hormones referred to as growth factors are locally acting intercellular messengers whose effects are not always related to stimulation of cell proliferation. The goal of the research described in this proposal is to identify some of the growth factors that play a role in lung development, and to determine their mechanisms of action. Growth factor mediated events can be viewed as having four components: the growth factor,the growth factor producing cell, the target cell, and the target cell's response. Initial characterization of such a pathway generally begins with the discovery of a specific growth factor or a specific cellular response. Such discoveries have led to the proposals presented here. The first will be to determine the role of a defined growth factor in an unknown cell-cell interaction. Specifically, we will characterize the regulation, structure and function of the lung-specific putative growth factor, irp. The irp gene and its gene product are related to the mammary oncogene int- l, which has been shown to encode a peptide growth factor that functions in specific events in mouse embryo development. Our second approach will be to determine the identity of the growth factors that function in an otherwise well defined Phase of lung development, specifically the maturation of the Type II alveolar pneumocyte. In these studies, we will study the regulation and function of the adipogenin gene and its product. Adipogenin, whose expression is controlled by growth factors, has been shown to be required for the targeting of differentiation in murine adipogenic cell lines. It is expressed abundantly in lungs; preliminary evidence suggests that it may be produced in Type II pneumocytes. Thus, adipogenin might be an important component of the mechanism by which these cells respond to growth factor stimulation. We will determine the role of adipogenin in the development of these cells, analyze the biochemical mechanisms by which these factors influence adipogenin gene expression, and characterize the effect of the growth factor on maintenance of the differentiated phenotype in lung cells expressing the gene.